Is CDON p.Asp258Glu (c.774C>A) pathogenic?

CDON p.Asp258Glu (c.774C>A) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). AlphaMissense: likely pathogenic (0.6479); Absent from gnomAD v4.1.

How common is CDON p.Asp258Glu (c.774C>A) in the general population?

CDON p.Asp258Glu (c.774C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDON p.Asp258Glu (c.774C>A)?

AlphaMissense predicts likely pathogenic (score 0.6479) — an in-silico prediction, not a clinical call.

CDON p.Asp258Glu

c.774C>A · rs777623487 · VCV2662258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6479 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6479	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -11.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDON
Protein: p.Asp258Glu
Coding: c.774C>A
MANE Select: NM_001378964
dbSNP: rs777623487
Type: single nucleotide variant
Location: chr11:126017242 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 258: a disulfide bond; the ig-like c2-type 3 domain

Full CDON gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDON p.Asp258= Likely benign ★ same residue
CDON c.3276+1G>T Uncertain significance ★★ same type
CDON c.640+1G>A Uncertain significance ★★ same type
CDON c.*1805A>G Uncertain significance ★★ same type
CDON c.*1816C>T Uncertain significance ★★ same type
CDON c.*2349A>C Uncertain significance ★★ same type
CDON c.*2377T>C Uncertain significance ★★ same type
CDON c.*2760A>G Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdon-p-asp258glu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown